A novel mutation at the N-terminal of SMN Tudor domain inhibits its interaction with target proteins

J Neurol. 2007 May;254(5):624-30. doi: 10.1007/s00415-006-0410-x. Epub 2007 Apr 6.


Although most patients with spinal muscular atrophy (SMA) are homozygous for deletion of the SMN1 gene, some patients bear one SMN1 copy with a subtle mutation. Detection of such an intragenic mutation may be helpful not only in confirming diagnosis but also in elucidating functional domains of the SMN protein. In this study, we identified a novel mutation in SMN1 of two Japanese patients with type I SMA. DHPLC and sequencing analysis revealed that they harbored a point mutation in SMN1 exon 3, 275G > C, leading to tryptophan-to-serine substitution at amino acid 92 (W92S) at the Nterminal of SMN Tudor domain. In-vitro protein binding assays showed that the mutation severely reduced interaction of the domain with SmB protein and fibrillarin, suggesting that it impairs the critical function of SMN. In conclusion, we reported here that a novel mutation, W92S, in the Tudor domain affects the interaction of SMN with the target proteins.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution*
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • DNA Mutational Analysis / methods
  • Family Health
  • Female
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics*
  • RNA-Binding Proteins / genetics*
  • Radioligand Assay / methods
  • SMN Complex Proteins
  • Serine / genetics
  • Spinal Muscular Atrophies of Childhood / genetics*
  • Survival of Motor Neuron 1 Protein
  • Tryptophan / genetics


  • Chromosomal Proteins, Non-Histone
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein
  • fibrillarin
  • Serine
  • Tryptophan